Cardiovascular disease is the leading cause of morbidity and mortality in the United States. Oxidative Stress and Inflammation play a pivotal role in atherogenesis. CANDIDATE: In the funded K24 Award (Year 4), the principal investigator has made excellent progress with respect to productivity (publications and procuring grants), mentoring and enhancing his research program. RESEARCH PLAN: In the present proposal, which aims to further strengthen his research program and mentoring in patient-oriented research, the principal investigator proposes the following studies: 1) The Effect of High dose Alpha tocopherol Supplementation on Oxidative Stress (OS), Inflammation and Carotid Atherosclerosis in Patients with Coronary artery disease;2) Monocyte Function and Inflammation in Type 1 Diabetes and its Modulation with Simvastatin therapy;3) The Effect of Simvastatin Therapy on Monocytic Inflammatory Markers and hsCRP Levels in Patients with the Metabolic Syndrome;4) A Dose-Response Effect of Lycopene supplementation on Biomarkers of OS;5) Effect of Alpha tocopherol and Gamma tocopherol Supplementation on Biomarkers of OS and Inflammation in Patients with the Metabolic Syndrome. Biomarkers of OS that will be analyzed include urinary F2-isoprostanes, LDL oxidative susceptibility;biomarkers of inflammation will include hs-CRP, SAA, plasma soluble cell adhesion molecules, monocyte superoxide anion release, cytokine release, adhesion to endothelium. MENTORING PLAN: These focused and cohesive clinical studies in Nutrition and Metabolism, in addition to the didactic courses and Mentored Clinical Research Training Program offered at UC-Davis will provide an excellent training ground for the junior faculty and clinical fellows in the area of patient-oriented research. Thus, studies outlined in this proposal will clearly enhance the long-term objectives of the principal investigator, since his major interest is in the area of lipoproteins, oxidative stress and inflammation in diabetes and atherosclerosis and their modulation.